Oncologic Benefits and Cardiovascular Risks of Pembrolizumab: Insights From a Nationwide Lung Adenocarcinoma Cohort.

BACKGROUND: Pembrolizumab improves survival in advanced lung adenocarcinoma, but potential cardiovascular toxicity remains. OBJECTIVES: This study evaluated the oncologic benefits and cardiovascular risks of pembrolizumab in a nationwide lung adenocarcinoma cohort. METHODS: We analyzed 39,192 patients newly diagnosed with lung adenocarcinoma between 2012 and 2019 using the nationwide cancer registry. We compared 573 patients treated with pembrolizumab within 1 year of diagnosis with 38,619 patients who were not treated within 3 years. The outcomes included all-cause mortality and myocardial infarction (MI), ischemic stroke (IS), heart failure (HF), pericarditis/myocarditis, and atrial fibrillation (AF) over a 3-year follow-up. RESULTS: During a median follow-up of 3.0 years (IQR: 1.0-3.0 years), 18,241 deaths, 574 MI, 1,157 IS, 2,777 HF, 852 pericarditis/myocarditis, and 1,601 AF events occurred. Model-based adjusted outcome curves showed lower all-cause mortality among users (adjusted P < 0.001) but higher incidences of IS, HF, and AF (adjusted P = 0.028, <0.001, and 0.048, respectively). Nonsignificant trends toward increased risks of MI and pericarditis/myocarditis were observed. Multivariable survival analyses, including Fine-Gray competing risk models for nonfatal cardiovascular outcomes, showed that pembrolizumab use was associated with lower all-cause mortality (HR: 0.77; 95% CI: 0.69-0.86) but with increased risks of IS (HR: 1.56, 95% CI: 1.10-2.23), HF (HR: 2.72, 95% CI: 2.24-3.30), and AF (HR: 1.47, 95% CI: 1.08-2.01); increases in MI and pericarditis/myocarditis were nonsignificant. CONCLUSIONS: Pembrolizumab was associated with lower all-cause mortality but higher risks of major cardiovascular events. These findings support vigilant cardio-oncologic monitoring in patients treated with pembrolizumab.